Kunitz-type protease inhibitor TFPI2 remodels stemness and immunosuppressive tumor microenvironment in glioblastoma.

Glioblastoma (GBM) tumors consist of multiple cell populations, including self-renewing glioblastoma stem cells (GSCs) and immunosuppressive microglia. Here we identified Kunitz-type protease inhibitor TFPI2 as a critical factor connecting these cell populations and their associated GBM hallmarks of stemness and immunosuppression. TFPI2 promotes GSC self-renewal and tumor growth via activation of the c-Jun N-terminal kinase-signal transducer and activator of transcription (STAT)3 pathway. Secreted TFPI2 interacts with its functional receptor CD51 on microglia to trigger the infiltration and immunosuppressive polarization of microglia through activation of STAT6 signaling. Inhibition of the TFPI2-CD51-STAT6 signaling axis activates T cells and synergizes with anti-PD1 therapy in GBM mouse models. In human GBM, TFPI2 correlates positively with stemness, microglia abundance, immunosuppression and poor prognosis. Our study identifies a function for TFPI2 and supports therapeutic targeting of TFPI2 as an effective strategy for GBM.

The fifth metatarsal base: anatomic evaluation regarding fracture mechanism and treatment algorithms.

Fractures occurring within the 1.5-cm proximal portion of the fifth metatarsal are commonly considered avulsion fractures. The exact mechanisms of such fractures are controversial. The present study focused on determining the likely mechanism of fracture according to the exact anatomy to allow for more successful treatment. The research sample included 10 frozen cadaveric specimens. The lateral band of the plantar fascia, peroneus brevis, and articular surface were identified and separated from their attachments, thereby splitting the fifth metatarsal base into zones A, B, and C. In zone A, the attachment of the plantar fascia was 6.6 ± 2.2 mm from the inferior aspect, 9.5 ± 2.9 mm from the proximal aspect, and 11.5 ± 0.9 mm from the lateral aspect. In zone B, the attachment of the peroneus brevis was 12.0 ± 2.2 mm from the inferior aspect, 10.2 ± 2.2 mm from the proximal aspect, and 11.5 ± 0.9 mm from the lateral aspect. Zone C was measured from the border of zone B and encompassed the articulation of the fifth metatarsal to the cuboid. We propose that fractures occurring in the most proximal end of the fifth metatarsal, zone A, are caused by a lateral band of plantar fascia and might be able to be treated conservatively by immobilization with weightbearing. We also propose that fractures occurring in zones B and C result from traumatic tension on peroneus brevis and might need to be treated with strict immobilization and non-weightbearing or open reduction internal fixation.